Fetal Diagn Ther 2006;21:528–531 Received: July 12, 2005 Accepted after revision: January 19, 2006 DOI: 10.1159/000095667 Published online: September 12, 2006 The Effectiveness of Adrenocorticotropin Repeated Doses in High Risk Pregnancies M. Klimek Department of Gynecology and Infertility Clinic of Jagiellonian University, Krakow , Poland Key Words higher newborn mass and length than patients who re- Adrenocorticotropin Preterm birth Oxytocinase ceived a series of three hormonal injections as well as Hormonal therapy control women who had no clinical or laboratory indica- tion for such therapy. Conclusions: ACTH-depot injection results in the oxytocinase increased serum level, a de- Abstract creased number of abortion and preterm deliveries and Objective: The aim of this study was to assess the effect prolonged duration of pregnancy. Single repeated doses of two kinds of adrenocorticotropin (ACTH)-depot re- of the ACTH-depot therapy had statistically signifi cant peated doses administered to pregnant women who un- better results in the prolongation of pregnancy, newborn derwent infertility treatment. Material and Methods: The mass and length than a serial hormonal dosage. study population included 424 pregnant women with Copyright © 2006 S. Karger AG, Basel singletons. Two hundred and forty-two women received repeated 0.5 mg doses of ACTH, whereas 182 women also were treated for infertility but did not receive any Introduction therapy. The ACTH-treated patients were subdivided into two subgroups: (1) 142 patients received only series The benefi cial effects of the antenatal ad r enocortico- of three 0.5 g ACTH-depot injections every other day in tropin (ACTH)-depot and corticosteroids have been the fi rst and/or second trimester with occasionally single known, respectively for more than 40 [1] and 30 years [2] , ACTH-depot doses in the third trimester, (2) 100 patients but still only a small part, i.e., 25% of potential patients received only single 0.5 mg ACTH-depot doses for the are exposed to the hormonal therapy. The prenatal ste- entire duration of pregnancy. Clinical symptoms of roid therapy is believed to mimic the exposure to endog- threatened abortion and preterm delivery as well as very enous corticosteroids, which can easily be done by the low or decreasing levels of serum oxytocinases were in- ACTH-depot therapy. What is more, the betamethasone dications for the hormonal therapy. Low oxytocinase or dexamethasone use is not recommended in cases of serum levels, recurrent abortion and preterm delivery gestational age !28 weeks or 134 weeks, multiple gesta- characterize pregnant women with hypothalamic insuf- tions, delivery likely in !48 h or 67 days, premature rup- fi ciency. Results: Women who received only single dos- ture of membranes, and fetal and maternal complications es of the ACTH-therapy for the entire duration of preg- (i.e., diabetes, hypertension, or infection) [3–6] . The men- nancy had a statistically signifi cant longer gestation, and tioned factors do not eliminate the ACTH-depot therapy © 2006 S. Karger AG, Basel Marek Klimek MD, PhD 1015–3837/06/0216–0528$23.50/0 Department of Gynecology and Infertility Clinic of Jagiellonian University Fax +41 61 306 12 34 23 Kopernik Str E-Mail [email protected] Accessible online at: PL–31-501 Krakow (Poland) www.karger.com www.karger.com/fdt Tel. +4812 424 8528, Fax +4812 424 8585, E-Mail [email protected] [7, 8] because it uses natural endogenous corticoids and The evaluation of neonate maturation according to K index is therefore safe and can be used multiply during all tri- (Klimek index) was performed [17] . The estimation of the follow- mesters of pregnancy, not only 67 days before labor. ing features was included: the distribution of lanugo, the presence of plantar creases, the range of breast nipple, the position of ex- Additionally, the hormonal and enzymatic production tremities, the size of elbow angle, and the range of the elbow dislo- in the placenta is crucial in the mutual maternal-fetal cation to the midline. The range of newborn maturity was deter- neuro-immuno-endocrinal conditionings, especially the mined using the scale of 0, 1 and 2 points K: well-matured 9–12 synthesis and the supply of the oxytocinase (cystinoami- points K, low-matured 6–8 points K and premature infant less than nopeptidase-CAP ) and isooxytocinase (CAP ) concen- 6 points K. 1 2 The oxytocinase serum levels (CAP) of pregnant women were trations in the mother’s blood. Both enzymes are induced analyzed according to the Tuppy and Nesvadba method modifi ed by the same neurohormones whose production increases by Klimek, described in former publications [14, 15] . The results as the pregnancy progresses. The biochemical method of are presented in international units: mol/l/min. pregnancy monitoring and the birth-term determination The distribution of variables in the examined groups of women checked with the use of the Shapiro-Wilk test showed that all of by the evaluation of oxytocinase (CAP ) and isooxytoci- 1 them were different from normal. Therefore, non-parametric test- nase (CAP 2 ) serum levels increasing until labor was used ing was employed. Statistical signifi cance between the groups was [9, 10] . Only the physiological depletion of the adaptive determined by the Kruskal-Wallis analysis of variance (ANOVA) possibility of the whole placenta before labor shifts the test. The Mann-Whitney U test was then used as applicable. The balance to the hormones, which has long been described Spearman rank test was used to evaluate interclass correlation coef- fi cients. All calculations were carried out with the use of STATIS- as an ‘enzymatic block’ basing on the example of the oxy- TICA software v. 6 (StatSoft, USA, 2001). tocin-oxytocinase system [11, 12] . On the basis of the changes in the maternal CAP 1 and CAP 2 levels one can, among other things, assess when fetal death might occur Results or whether pregnancy is threatened only by abortion or preterm birth. When treatment is undertaken, the en- Table 1 presents the characteristics of study groups zymes become the most important element of its moni- I–III. No differences were found between these groups in toring, particularly in the hormone stimulation of the the mother’s age, the obstetrical history and oxytocinase maturation of the fetal respiratory system [1, 13–16] . and isooxytocinase serum levels before labor, the range The aim of this study was to determine the effect of of newborn maturation (K index) and the postpartum two kinds of repeated 0.5 mg doses of the ACTH-depot adaptation (Apgar) score. The average newborns’ ages, therapy: (1) series of three injections every other day and masses and lengths differed statistically and were ob- (2) single doses with an interval of at least 1 week between served to be the highest in group II and the lowest in group injections. The differences between them have not been I. Group II was statistically signifi cantly 1.54 more fre- previously reported. The clinical effect of a single 0.5 mg quently administered single doses of the ACTH-depot dose of ACTH-depot lasts ca. 48 h while the series of three and the average pregnancy duration time was statistical- doses covers 1 week. Low or decreasing levels of oxytoci- ly signifi cant 4.3 days elongated, the fetuses mass was nases (CAP 1 and CAP 2 ) or clinical symptoms of threat- 247 g higher and the lengths were 1.4 cm longer than in ened gestation is an indication for the ACTH-depot ther- group I. apy. Average values reached by group III, without the ad- ministration of the ACTH-depot therapy, were between the values reached by groups I and II with respect to the Materials and Methods pregnancy duration time and the newborn state range, but represented the statistically signifi cant highest CAP 1 Prospective study performed between 2001 and 2004 included and CAP prepartal value. a group of 424 women with a singleton pregnancy aged 30.1 8 4.7 2 (19–44) years, which were classifi ed into three following groups: The control group in comparison to I and II subgroup Group I = 142 pregnant women treated by a series of three 0.5 mg women had two times fewer abortions in the past and the ACTH-depot injections every other day with single supplementary highest prepartal levels of CAP 1 and CAP 2 with the same doses in the third trimester of pregnancy; Group II = 100 pregnant newborn adaptation and maturity points ( table 1 ). In women treated only by single ACTH-depot doses not more fre- treated women better results were obtained in the single quently than once a week for the entire duration of pregnancy; Group III = 182 women also after the infertility treatment, who did dosage group, however, the rising of the dose caused the not require the substitution hormonal therapy (control group). In decreasing of the number of cases of cervical cerclages all patients informed consent was obtained. and the increasing number of cases of spontaneous onsets Effectiveness of Adrenocorticotropin in Fetal Diagn Ther 2006;21:528–531 529 High Risk Pregnancies Table 1. The characteristics of prospectively studied groups I, II and III Groups I (n = 142) II (n = 100) III control group (n = 182) Mothers’ average age, years 29.684.3 (21–44) 31.084.6 (20–43) 30.085.1 (19–46) Number of gestations 1.981.3 (1–8) 2.081.2 (1–8) 1.881.3 (1–7) Number of deliveries 1.280.6 (1–4)III 1.280.6 (1–4)III 1.480.8 (1–5)I, II Number of abortions 0.781.0 (0–7) 0.880.9 (0–5) 0.480.8 (0–4) Number of children 1.280.5 (0–4) 1.280.6 (0–5) 1.480.7 (0–4) Total number of ACTH injections during gestation 5.282.8 (1–14)II 9.183.5 (1–19)I – III III I, II CAP1, ␮mol/l/min 7.782.5 (1.8–15.6) 7.882.5 (1.8–14.0) 8.982.4 (3.4–16.2) III I CAP2, ␮mol/l/min 6.481.8 (2.8–12.0) 6.581.8 (2.8–12.5) 6.881.9 (3.2–12.8) Length of gestation, days 270.7822.0 (222–305)II 275.0811.0 (230–303)I 272.6812.0 (214–306) Newborn mass, g 3,2308504 (1,510–4,200)II, III 3,4778420 (1,840–4,400)I, III 3,3418480 (1,780–4,350)I, II Length, cm 53.683.2 (42–64)I, II 55.082.5 (46–60)I, III 54.482.6 (43–59)I, II Apgar, points 9.580.8 (4–10) 9.780.9 (4–10) 9.781.5 (4–10) Klimek, points 8.881.6 (4–12) 8.981.7 (4–11) 8.881.7 (3–12) I–III The difference was statistically signifi cant (p < 0.05).